Phase II Anetumab Ravtansine in Pre-treated Mesothelin-expressing Pancreatic Cancer

NCT03023722 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 1608018265
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 3

Brief Summary

The primary objective of this study is to:

• Test the activity/response rate per RECIST 1.1 criteria of anetumab ravtansine in patients with advanced pancreatic cancer who stain for mesothelin expression The secondary objectives of this study are to:
• Time to Progression (TTP) defined as time from study treatment to RECIST 1.1 progression, or death (others going off study will be censored)
• Toxicity in pancreatic cancer patients (at 6.5 mg/kg dose)

Conditions

Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

• Response Rate as Measured Per RECIST 1.1 Criteria

  Primary efficacy will be assessed based on radiological tumor evaluation by contrast-enhanced computed tomography (CT) or contrast-enhanced magnetic resonance imaging (MRI) of chest/abdomen/pelvis. Contrast enhanced RECIST 1.1 scan will be done at Prescreening. Said pre-screen scan will be the baseline measure. RECIST 1.1 Scans will be done every 6 weeks for the first 6 months after the start of treatment, or more frequently if clinically indicated, every 9 weeks until the end of year 2 and every 12 weeks thereafter until disease progression or end of study, whichever comes first.

  From start of treatment until disease progression or death (up to 3 years).

Secondary Outcomes (2)

• Time to Progression

  From start of treatment until disease progression or death (up to 3 years).

• Drug Toxicity

  From start of treatment until disease progression or death (up to 3 years).

Study Arms (1)

All Subjects

EXPERIMENTAL

Patients with advanced metastatic pancreatic cancer who have measurable disease

Drug: anetumab ravtansine

Interventions

anetumab ravtansine DRUG

Patients will receive anetumab ravtansine IV infusion at a dose of 6.5 mg/kg (recommended Phase II dose) on Day 1 of a 21-day cycle

All Subjects

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eligibility criteria for prescreening
• Must have had at least one and not more than two prior chemotherapy regimens for advanced disease (neoadjuvant or adjuvant chemotherapy would not be counted as a line of therapy). If prior radiation, measurable lesion outside radiation portal.
• Written informed consent for prescreening.
• Unresectable locally advanced or metastatic pancreatic cancer, confirmed by histology
• Availability of archival or fresh tissue for testing of mesothelin expression level.
• Note: Archival tissue is preferred and fresh biopsy should only be obtained if no archival tissue is available and if in the investigator's judgement, there is no additional risk for the patient's safety. Patients with a sarcomatoid histology are not expected to have mesothelin overexpression and should not enter prescreening.
• Age ≥ 18 years.
• Life expectancy of at least 3 months.
• No prior treatment with anetumab ravtansine (or any other mesothelin-based therapy)
• Eligibility criteria for full study
• Written informed consent for full study.
• Histological documentation of overexpressing mesothelin at the moderate (2+) or stronger (3+) level in at least 30% of tumor cells as determined by IHC.
• Unresectable locally advanced or metastatic pancreatic cancer
• At least one but not more than two prior chemotherapy regimens with progression or documented intolerance (neoadjuvant or adjuvant chemotherapy would not be counted as a line of therapy).
• Patients must have at least 1 measurable lesion according to RECIST v 1.1

You may not qualify if:

• Previous assignment to treatment during this study. Patients permanently withdrawn from study participation will not be allowed to re-enter the study.
• Previous (within 5 drug half-lives - if drug half-life in subjects is known - or 28 days, whichever is shorter, before the start of study treatment) or concomitant participation in another clinical study with investigational medicinal product(s) (IMP\[s\]).
• Patients with corneal epitheliopathy or any eye disorder that may predispose the patients to this condition at the discretion of the investigator.
• Previous or concurrent cancer that is distinct in primary site or histology within 5 years. Exceptions: curatively treated
• Cervical cancer in situ.
• Non-melanoma skin cancer.
• Superficial bladder tumors (Non-invasive tumor \[Ta\], Carcinoma in situ \[Tis\] and Tumor invades lamina propria \[T1\]).
• Major surgery, open biopsy or significant traumatic injury within 28 days before the start of study treatment.
• Pregnant or breast-feeding patients. Women of childbearing potential must have a serum pregnancy test performed a maximum of 7 days before the start of study treatment, and a negative result must be documented before the start of study treatment.
• Pre-existing cardiac conditions as outlined below:
• Congestive heart failure ≥ New York Heart Association (NYHA) class 2.
• Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months). Myocardial infarction less than 6 months before the start of study treatment.
• Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted).
• Clinically significant uncontrolled hypertension (systolic blood pressure \> 150 mmHg or diastolic pressure \> 90 mmHg despite optimal medical management).
• Arterial thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), or venous pulmonary embolism within 6 months before the start of study treatment; venous thrombotic events such as deep vein thrombosis within 3 months before the start of study treatment.

Sponsors & Collaborators

• Yale University: lead
• Bayer: collaborator

Study Sites (3)

Yale Cancer Center

New Haven, Connecticut, 06510, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901-2163, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

anetumab ravtansine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Limitations and Caveats

Premature termination may occur if risk-benefit ratio is unacceptable due to: safety findings, results of parallel clinical studies and results of parallel animal studies AND if the study does not suggest a completion within a reasonable time frame.

Results Point of Contact

• Title: Stacey Stein, MD
• Organization: Yale University

stacey.stein@yale.edu

203 737-1600

Study Officials

• Stacey Stein, MD

  Yale Cancer Center, Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2017
• First Posted: January 18, 2017
• Study Start: May 11, 2017
• Primary Completion: August 6, 2019
• Study Completion: December 11, 2019
• Last Updated: October 28, 2021
• Results First Posted: January 22, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)